Mercury vapor (HgO) and mercury containing compounds are extremely toxic substances. Recent studies point to dental amalgam as a point source of HgO. This has lead to speculation and concern regarding the effect of amalgam on the health of both the dental practitioner and the patient. While there is some dispute concerning the actual amount of mercury released from amalgam and absorbed into the body, there is universal agreement that the organic forms of mercury account for most of the ingested and absorbed mercury. Therefore, the objective of this investigation is to conduct a comprehensive study of the effect of organic mercury on the human immune system and to determine the mechanisms by which the metal compromises immunological function. The fundamental hypothesis to be tested is that exposure to mercury may lead to immunological abnormality that either directly or indirectly compromises the health of the exposed individual. The specific aims of this proposal are: (1) To determine if exposure of cells to low concentrations of inorganic mercury exacerbate the immunotoxic effects of organic mercury. Furthermore, we will extend these to determine if other forms of organic mercury are immunotoxic and if inorganic mercury alters the toxicity of these chemical species as well. In these studies we will determine the relative immunotoxicity of MeHg, ethyl mercury and phenyl mercury and determine if all effects on T-cell responses require monocytes. (2) To determine if mercuric compounds alter monocyte function and to explore the basis for the heightened sensitivity of monocytes to the toxic effects of mercury. We plan to determine the basis for the requirement of monocytes in mercury-mediated alterations in T-cell responsiveness. Also, we will test the hypothesis that the differences in lymphocyte and monocyte sensitivity to organic mercury is due to its rapid bioconversion to Hg++, which is a catalase dependent reaction. (3) To define the molecular basis for the immunomodulatory effects of organic mercury and the basis for the relative sensitivities of lymphoid cells to organic mercury. We will test the hypothesis that the mechanism by which mercury alters lymphocyte responsiveness is via the alteration in GSH and/or thiol status of the cell. (4) To develop an in vivo model system to study the immunotoxic effects of mercury on human lymphoid cells. We will utilize the SCID mouse system to extend our in vitro observations to an in vivo format that allows for biotransformations and "sinks", to study the immunotoxicity of organic mercury, HgCl2 and HGO. Together, the results of these studies will further our understanding of mercury immunotoxicity. Furthermore, they will provide a basis for understanding the health implication associated with the use, abuse and disposal of these noxious compounds.